|Budget Amount *help
¥3,600,000 (Direct Cost : ¥3,600,000)
Fiscal Year 1999 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1998 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1997 : ¥1,700,000 (Direct Cost : ¥1,700,000)
A process of carcinogenesis in rat submandibular gland (SMG), following the 2%DMBA containing sponge pellet insertion, was studied by the use of several histochemical markers and RT-PCR. K8.12 cytokeratin, epidermal growth factor, endothelin-3 and S-100 protein were used for the imunohistochemical markers of salivary gland duct. Calponin was used for the imunohistochemical marker of mioepithelial cells. Proliferating cell nuclear antigen imunohistochemistry and ィイD13ィエD1H-thymidine auto-radiograph were used to obtain proliferating potential. Basis fibroblast growth factor (bFGF) and its receptor (FGFr), and c-erbB-2 were studied as oncogene products.
During the carcinogenesis, proliferating cells were found in several kinds of ductal cells, though acinar compartment including myoepithelial cells showed no or minimal proliferating protential. In the histological patterns of carcinoma in rat SMG, the differentiation and/or conduction of modified myoepithelial cells may deeply influenced to form tubro-ductal structures in adenocarcinoma. There were no calponin positive modified myoepithelial cells found in squamous cell carcinoma, through in the adenomacarcinoma, they were arranged in the basal layer of the proliferating and dysplastic tubro-ductal structures.
In the variation of oncogene products during carinogenesis, bFGF and FGFr were enhanced their immunohistochemical expression in the tumor nest and coexisted in the same tumor cells. These result may suggest that, bFGF may stimulate carcinogenesis by autocrin and/or paracrin pathway. Furthermore, a progression of carcinogenesis brought to increase of c-erbB-2 mRNA level. RT-PCR product of c-erbB-2 was absent in normal SMG and 3 weeks of carnogenesis but showed harlf and all cases in 6 weeks and in 12 weeks specimens, respectively. Excessive c-erbB-2 prot-oncogene product may be one of a course for SMG carcinogenesis following DMBA administration.